The etiology of upper gastrointestinal bleeding(UGIB)varies by age,from newborns to adolescents,with some of the causes overlapping between age groups.While particular causes such as vitamin K deficiency and cow’s mi...The etiology of upper gastrointestinal bleeding(UGIB)varies by age,from newborns to adolescents,with some of the causes overlapping between age groups.While particular causes such as vitamin K deficiency and cow’s milk protein allergy are limited to specific age groups,occurring only in neonates and infants,others such as erosive esophagitis and gastritis may be identified at all ages.Furthermore,the incidence of UGIB is variable throughout the world and in different hospital settings.In North America and Europe,most UGIBs are nonvariceal,associated with erosive esophagitis,gastritis,and gastric and duodenal ulcers.In recent years,the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries.However,variceal bleeding still predominates in certain parts of the world,especially in South Asia.The most severe hemorrhage arises from variceal bleeding,peptic ulceration,and disseminated intravascular coagulation.Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients.Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings,the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIBincludes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability,followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis inthe pediatric population because some of them are unique to children. Endoscopic techniques are of significantdiagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally,surgical treatment is reserved for the most severe bleeding.展开更多
Splenic hamartomas(SHs)are uncommon,benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images,at surgery,or at autopsy.Since the first case description,in 1861,less than 50 pedi...Splenic hamartomas(SHs)are uncommon,benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images,at surgery,or at autopsy.Since the first case description,in 1861,less than 50 pediatric SH cases have been reported in the literature.In this article,we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH.These lesions in children were shown to cause symptoms more often than in the adult population.The observed SH sizes in children ranged from a few millimeters to 18 cm,and the symptomatic lesions were mostly larger or multiple.The most common clinical finding was splenomegaly.Signs of hypersplenism were present in children with a single SH larger than 4.5 cm(diameter range:4.5-18.0 cm)and in those with multiple hamartomas,ranging from a few millimeters to 5 cm.Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia,thrombocytopenia,or pancytopenia.Other symptoms and signs included abdominal pain,recurrent infections,fever,night sweats,lethargy,growth retardation,and weight loss.The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach.However,the final diagnosis of SH relies on histopathological evaluation.Surgery,including total or partial splenectomy(PS),is the mainstay of SH management.Milickovic M et al.Splenomas in children WJCC https://www.wjgnet.com 1910 April 16,2024 Volume 12 Issue 11 Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH.In the majority of pediatric patients with symptomatic SH,resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.展开更多
BACKGROUND Anaphylaxis is a life-threatening condition that develops as a reaction to exposure to an allergen which can be found in common foods such as cow's milk,egg,fish,and nuts in children.The use of an intra...BACKGROUND Anaphylaxis is a life-threatening condition that develops as a reaction to exposure to an allergen which can be found in common foods such as cow's milk,egg,fish,and nuts in children.The use of an intramuscular adrenaline auto-injector(AAI)is considered the most essential treatment in these situations and parents and caregivers are always encouraged to carry this device for use in an emergency which commonly takes place in public places such as restaurants,schools,and parks,where medical staff are not guaranteed to be available.However,previous studies,in different settings,have reported underuse of the AAI by parents.AIM To explore the reasons for underutilisation of the AAI in our community.METHODS A cohort of parents attending the paediatric allergy clinic at Al Ain Hospital in the United Arab Emirates completed a questionnaire survey aimed at assessing their understanding and knowledge of their child's allergy management,including their aptitude with the use of the AAI,as well as their competence and comfort in providing this treatment in an emergency.RESULTS Of 47 parents participating in the study,39 were Emirati parents(83%and most parents who completed the survey were mothers(66%).As expected,food was the main cause of allergic reactions requiring prescription of the auto-injector device.Tree nuts and peanuts were noted to be the most common offending food in these children(62%and 38%,respectively).A doctor provided demonstrations and training on using the auto-injector device to 94%of the parents.More than two-thirds of the parents and caregivers(79%)were deemed knowledgeable on the indication for use of the device.Reluctance to administer the device was expressed by many of the parents,despite their satisfaction with the coaching they received on using the device in the study.CONCLUSION Ongoing coaching and teaching of parents on use of the AAI is paramount.However,this should be carried out together with psychological support to aid the parents to eliminate their hesitancy and acquire sufficient confidence in using the device when needed.Group teaching and sharing experiences is an excellent educational technique in a non-formal setting.Paediatric clinic play therapists can also have a role in needle phobia desensitisation for parents and children.More research is needed to explore the lack of empowerment and other reasons behind their fear and anxiety in using the device to plan effective interventions.展开更多
The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievem...The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.展开更多
The most common digestive system(DS)cancers,including tumors of the gastrointestinal tract(GIT)such as colorectal cancer(CRC),gastric cancer(GC)and esophageal cancer(EC)as well as tumors of DS accessory organs such as...The most common digestive system(DS)cancers,including tumors of the gastrointestinal tract(GIT)such as colorectal cancer(CRC),gastric cancer(GC)and esophageal cancer(EC)as well as tumors of DS accessory organs such as pancreatic and liver cancer,are responsible for more than one-third of all cancerrelated deaths worldwide,despite the progress that has been achieved in anticancer therapy.Due to these limitations in treatment strategies,oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity.These studies led to new molecular target-driven therapeutic approaches.Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3(B7-H3)among the most common cancers of the GIT,including CRC,GC,and EC,whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal.This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms,and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways,such as Janus kinase 2/signal transducer and activator of transcription 3,phosphatidylinositol 3-kinase/protein kinase B,extracellular signal-regulated kinase,and nuclear factor-κB.B7-H3 exerts an important role in progression,metastasis and resistance to anticancer therapy in these tumors.In addition,the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response.Accordingly,it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response,impaired tumor progression,invasion,angiogenesis,and metastasis and decreased resistance to anticancer therapy.Finally,the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis.In this review,we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.展开更多
Gestational diabetes mellitus(GDM)is one of the most common metabolic disorders of pregnancy and can cause short-and long-term adverse effects in both pregnant women and their offspring.However,the etiology and pathog...Gestational diabetes mellitus(GDM)is one of the most common metabolic disorders of pregnancy and can cause short-and long-term adverse effects in both pregnant women and their offspring.However,the etiology and pathogenesis of GDM are still unclear.As a metabolic disease,GDM is well suited to metabolomics study,which can monitor the changes in small molecular metabolites induced by maternal stimuli or perturbations in real time.The application of metabolomics in GDM can be used to discover diagnostic biomarkers,evaluate the prognosis of the disease,guide the application of diet or drugs,evaluate the curative effect,and explore the mechanism.This review provides comprehensive documentation of metabolomics research methods and techniques as well as the current progress in GDM research.We anticipate that the review will contribute to identifying gaps in the current knowledge or metabolomics technology,provide evidence-based information,and inform future research directions in GDM.展开更多
BACKGROUND:To promote the shared decision-making(SDM)between patients and doctors in pediatric outpatient departments,this study was designed to validate artificial intelligence(AI)-initiated medical tests for childre...BACKGROUND:To promote the shared decision-making(SDM)between patients and doctors in pediatric outpatient departments,this study was designed to validate artificial intelligence(AI)-initiated medical tests for children with fever.METHODS:We designed an AI model,named Xiaoyi,to suggest necessary tests for a febrile child before visiting a pediatric outpatient clinic.We calculated the sensitivity,specificity,and F1 score to evaluate the efficacy of Xiaoyi’s recommendations.The patients were divided into the rejection and acceptance groups.Then we analyzed the rejected examination items in order to obtain the corresponding reasons.RESULTS:We recruited a total of 11,867 children with fever who had used Xiaoyi in outpatient clinics.The recommended examinations given by Xiaoyi for 10,636(89.6%)patients were qualified.The average F1 score reached 0.94.A total of 58.4%of the patients accepted Xiaoyi’s suggestions(acceptance group),and 41.6%refused(rejection group).Imaging examinations were rejected by most patients(46.7%).The tests being time-consuming were rejected by 2,133 patients(43.2%),including rejecting pathogen studies in 1,347 patients(68.5%)and image studies in 732 patients(31.8%).The difficulty of sampling was the main reason for rejecting routine tests(41.9%).CONCLUSION:Our model has high accuracy and acceptability in recommending medical tests to febrile pediatric patients,and is worth promoting in facilitating SDM.展开更多
From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same ti...From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.展开更多
Introduction:Transcatheter closure is an alternative to ventricular septal defect(VSD)occlusion surgery.Nit-Occlud LêVSD coil is a new device yet to be evaluated.The study aimed to evaluate immediate and midterm ...Introduction:Transcatheter closure is an alternative to ventricular septal defect(VSD)occlusion surgery.Nit-Occlud LêVSD coil is a new device yet to be evaluated.The study aimed to evaluate immediate and midterm results after transcatheter closure with the Nit-Occlud LêVSD device.Methods:The retrospective analysis included 30 patients with VSD referred for closure during the period from October 2015 to December 2020.Results:At the time of intervention,the patients’mean age and body weights were 7.5±5.6 years and 29.3±19.1 kg.The majority of the defects had perimembranous location(24/30),four defects had muscular and two outlet subaortic position.The mean effective right-side diameter of the VSDs was 3.6±1.3 mm.Single ventricular fibrillation,device embolization,and hemolysis developed in different patients and were successfully treated.None of the patients had a complete atrioventricular block.The coil was successfully placed in 25/30(83.3%)patients.The majority of the devices were 10 mm×6 mm(11/25)and 12 mm×8 mm(8/25)in size.Two patients required the implantation of a second device.The follow-up period was 2.1±1.4 years.Complete VSD closure was achieved in 48%of cases immediately after the intervention,74%during 2.1±1.6 months after the procedure,and 81%over follow-up.The remaining patients had a trivial residual defect.During the follow-up,approximately one-third of patients developed trivial aortic and mitral valve regurgitation,and half of the patients acquired trace/mild tricuspid regurgitation.Standardized(z-score)left ventricular end-diastolic diameter(0.15±0.37 vs.0.92±0.82,p=0.005)and left atrium dimension(0.47±0.58 vs.1.89±1.11,p=0.005),as well as the left atrium to aortic root ratio(1.2±0.1 vs.1.4±0.2,p=0.005)showed a significant decrease over follow-up related to the period before intervention.Conclusion:Intervention with Nit-OccludLêVSD coil showed appropriate results regarding VSD closure rate,complications,and chamber remodeling.The introduction of this device into clinical practice is a significant step forward in transcatheter perimembranous VSD occlusion.展开更多
Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of ID...Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.展开更多
Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival outcomes.The B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,...Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival outcomes.The B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,including PC,with low or absent expression in healthy tissues.By modulating various immunological and nonimmunological molecular mechanisms,B7-H3 may influence the progression of PC.However,the impact of B7-H3 on the survival of patients with PC remains a subject of debate.Still,most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in PC.Furthermore,it has been demonstrated that B7-H3 stimulates the migration,invasion,and metastasis of PC cells,and enhances resistance to chemotherapy.In preclinical models of PC,B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibodydependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor site.Finally,PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical studies.This review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research.展开更多
Objective: To determine differences in case fatality rates between children with and without Down syndrome. Study design: We used the Pediatric Health Information System (PHIS) database, which includes demographic and...Objective: To determine differences in case fatality rates between children with and without Down syndrome. Study design: We used the Pediatric Health Information System (PHIS) database, which includes demographic and diagnostic data from freestanding children’s hospitals. Using Poisson regression, we determined the risk of mortality from sepsis for children with Down syndrome, after controlling for potential confounding factors. Results: A total of 35,645 patients met our inclusion criteria, of which 3936 (11%) died during hospitalization. Altogether, 620 of the included patients also had a diagnosis of Down syndrome; 106 (17%) of these died during hospitalization. Children with Down syndrome had significantly elevated risk of mortality (mortality rate ratio = 1.30; 95%confidence interval = 1.06 to 1.59) after adjusting for potential confounding factors including demographics, pathogens, and concomitant conditions. Conclusions: Children with Down syndrome and sepsis have elevated risk of mortality. These findings have implications for treatment decisions, communications about prognosis, and future research.展开更多
Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included ro...Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein- Barr virus (EBV) serology, urine, stool or blood cultures, chest X- ray and tuberculin probe. Results: In 131 (70% ) patients diagnosis was established, and 70 (37.8% )- had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9% ), Kawasaki disease in 12 (6.4% ), malignant diseases in 12 (6.4% ) and miscellaneous conditions in 15 (8.1% ) patients. In the remaining 54 (30% ) patients, diagnosis was not established and most of them had self- limited disease. During the investigation, 26 (14% ) patients developed serious organ dysfunction and five patients (two with virusassociated haemophagocytic syndrome, one with VL and two unknown) died. Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary- care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.展开更多
To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an essential treatment for various malignant hematological diseases,non-malignant hematological diseases,immunodeficiency diseases,and meta...To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an essential treatment for various malignant hematological diseases,non-malignant hematological diseases,immunodeficiency diseases,and metabolic diseases in children.[1]During the period of post allo-HSCT immunodeficiency before complete immune reconstitution,transplant recipients having a compromised immune system are more susceptible to infectious diseases than the general population.Therefore,revaccination plays a crucial role in protecting pediatric allo-HSCT recipients from vaccine-preventable diseases.Inactivated vaccines are generally safer and can be administered starting from 6–12 months after transplantation.Live-attenuated vaccines should be administered at least 24 months after transplantation and at least one year after stopping immunosuppressive drugs due to the risk of severe vaccine-induced infection when administered with immunosuppressive agents.[2,3]展开更多
Background Developmental delay(DD)poses challenges to children's overall development,necessitating early detection and intervention.Existing screening tools in China focus mainly on children with developmental iss...Background Developmental delay(DD)poses challenges to children's overall development,necessitating early detection and intervention.Existing screening tools in China focus mainly on children with developmental issues in two or more domains,diagnosed as global developmental delay(GDD).However,the recent rise of early childhood development(ECD)concepts has expanded the focus to include not only those with severe brain development impairments but also children who lag in specific domains due to various social-environmental factors,with the aim of promoting positive development through active intervention.To support this approach,corresponding screening tools need to be developed.Methods The current study used a two-phase design to develop and validate the Parent-Reported Indicator of Developmental Evaluation for Chinese Children(PRIDE)tool.In Phase 1,age-specific milestone forms for PRIDE were created through a survey conducted in urban and rural primary care clinics across four economic regions in China.In Phase 2,PRIDE was validated in a community-based sample.Sensitivity and specificity of both PRIDE and Ages and Stages Questionnaires(ASQ)-3 were estimated using inverse probability weights(IPW)and multiple imputation(MI)to address planned and unplanned missing data.Results In Phase 1 involving a total of 1160 participants aged 1 to 48 months,63 items were selected from the initial item pool to create 10 age-specific PRIDE forms.Our Phase 2 study included 777 children within the same age range.PRIDE demonstrated an estimated sensitivity and specificity of 83.3%[95%confidence interval(CI):56.8%–100.0%]and 84.9%(95%CI:82.8%–86.9%)in the identification of DD.Conclusion The findings suggest that PRIDE holds promise as a sensitive tool for detecting DD in community settings.展开更多
Background Asthma has been a global problem,especially in children.We aim to evaluate the contemporary prevalence and influencing factors of asthma among children aged 3–7 years in Shanghai,China.Methods A random sam...Background Asthma has been a global problem,especially in children.We aim to evaluate the contemporary prevalence and influencing factors of asthma among children aged 3–7 years in Shanghai,China.Methods A random sample of preschool children was included in this study.The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma.Multivariable logistic regression models were used to evaluate the associations between independent variables and childhood asthma.Results Of 6389 preschool children who were invited to take part in this study,6163(response rate:96.5%)completed the questionnaire and were included in the analysis.The overall prevalence of asthma was 14.6%which increased more than six folds from 2.1%in 1990.Being male,younger age,preterm delivery,being born in spring or autumn,being delivered by elective cesarean section without indication,miscarriage,high socioeconomic status,having allergy history,and exposure to passive smoking,latex paint,and dust were potential risk factors for childhood asthma.Spending more time outdoors(>30 min/day),having indoor plants,and cleaning rooms more frequently were potential protective factors.Conclusions The prevalence of childhood asthma in Shanghai has increased dramatically during the past three decades.The findings about risk and protective factors of childhood asthma could be used to develop appropriate strategies to prevent and control childhood asthma in Shanghai and in other similar metropolitan cities.展开更多
Precision medicine requires coordinated and integrated evidence-based combinatorial approaches so that diagnosis and treatment can be tailored to the individual patient.In this context,the treatment approach to mild o...Precision medicine requires coordinated and integrated evidence-based combinatorial approaches so that diagnosis and treatment can be tailored to the individual patient.In this context,the treatment approach to mild obstructive sleep apnea(OSA)is fraught with substantial debate as to what is mild OSA,and as to what constitutes appropriate treatment.As such,it is necessary to first establish a proposed consensus of what criteria need to be employed to reach the diagnosis of mild OSA,and then examine the circumstances under which treatment is indicated,and if so,whether and when anti-inflammatory therapy(AIT),rapid maxillary expansion(RME),and/or myofunctional therapy(MFT)may be indicated.展开更多
Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses...Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses to human society.The overall crude mortality rate is 1-3%.Although pediatric deaths from COVID-19 are rare,they do occur,as over 9,000 children have died from COVID-19 globally to date[1].With the gradual and broad application of COVID-19 vaccines around the world,the rising proportion of cases among children and unvaccinated young adults demands attention.According to World Health Organization surveillance data.展开更多
Astroglia are integral to brain development and the emergence of neurodevelopmental disorders.However,studying the pathophysiology of human astroglia using brain organoid models has been hindered by ineficient astrogl...Astroglia are integral to brain development and the emergence of neurodevelopmental disorders.However,studying the pathophysiology of human astroglia using brain organoid models has been hindered by ineficient astrogliogene-sis.In this study,we introduce a robust method for generating astroglia-enriched organoids through BMP4 treatment during the neural differentiation phase of organoid development.Our RNA sequencing analysis reveals that astroglia developed within these organoids exhibit advanced developmental characteristics and enhanced synaptic functions compared to those grown under traditional two-dimensional conditions,particularly highlighted by increased neu-rexin(NRXN)-neuroligin(NLGN)signaling.Cell adhesion molecules,such as NRXN and NLGN,are essential in regulat-ing interactions between astroglia and neurons.We further discovered that brain organoids derived from human embryonic stem cells(hESCs)harboring the autism-associated NLGN3 R451C mutation exhibit increased astroglio-genesis.Notably,the NLGN3 R451C astroglia demonstrate enhanced branching,indicating a more intricate morphol-ogy.Interestingly,our RNA sequencing data suggest that these mutant astroglia significantly upregulate pathways that support neural functions when compared to isogenic wild-type astroglia.Our findings establish a novel astroglia-enriched organoid model,offering a valuable platform for probing the roles of human astroglia in brain development and related disorders.展开更多
文摘The etiology of upper gastrointestinal bleeding(UGIB)varies by age,from newborns to adolescents,with some of the causes overlapping between age groups.While particular causes such as vitamin K deficiency and cow’s milk protein allergy are limited to specific age groups,occurring only in neonates and infants,others such as erosive esophagitis and gastritis may be identified at all ages.Furthermore,the incidence of UGIB is variable throughout the world and in different hospital settings.In North America and Europe,most UGIBs are nonvariceal,associated with erosive esophagitis,gastritis,and gastric and duodenal ulcers.In recent years,the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries.However,variceal bleeding still predominates in certain parts of the world,especially in South Asia.The most severe hemorrhage arises from variceal bleeding,peptic ulceration,and disseminated intravascular coagulation.Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients.Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings,the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIBincludes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability,followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis inthe pediatric population because some of them are unique to children. Endoscopic techniques are of significantdiagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally,surgical treatment is reserved for the most severe bleeding.
文摘Splenic hamartomas(SHs)are uncommon,benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images,at surgery,or at autopsy.Since the first case description,in 1861,less than 50 pediatric SH cases have been reported in the literature.In this article,we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH.These lesions in children were shown to cause symptoms more often than in the adult population.The observed SH sizes in children ranged from a few millimeters to 18 cm,and the symptomatic lesions were mostly larger or multiple.The most common clinical finding was splenomegaly.Signs of hypersplenism were present in children with a single SH larger than 4.5 cm(diameter range:4.5-18.0 cm)and in those with multiple hamartomas,ranging from a few millimeters to 5 cm.Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia,thrombocytopenia,or pancytopenia.Other symptoms and signs included abdominal pain,recurrent infections,fever,night sweats,lethargy,growth retardation,and weight loss.The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach.However,the final diagnosis of SH relies on histopathological evaluation.Surgery,including total or partial splenectomy(PS),is the mainstay of SH management.Milickovic M et al.Splenomas in children WJCC https://www.wjgnet.com 1910 April 16,2024 Volume 12 Issue 11 Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH.In the majority of pediatric patients with symptomatic SH,resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.
文摘BACKGROUND Anaphylaxis is a life-threatening condition that develops as a reaction to exposure to an allergen which can be found in common foods such as cow's milk,egg,fish,and nuts in children.The use of an intramuscular adrenaline auto-injector(AAI)is considered the most essential treatment in these situations and parents and caregivers are always encouraged to carry this device for use in an emergency which commonly takes place in public places such as restaurants,schools,and parks,where medical staff are not guaranteed to be available.However,previous studies,in different settings,have reported underuse of the AAI by parents.AIM To explore the reasons for underutilisation of the AAI in our community.METHODS A cohort of parents attending the paediatric allergy clinic at Al Ain Hospital in the United Arab Emirates completed a questionnaire survey aimed at assessing their understanding and knowledge of their child's allergy management,including their aptitude with the use of the AAI,as well as their competence and comfort in providing this treatment in an emergency.RESULTS Of 47 parents participating in the study,39 were Emirati parents(83%and most parents who completed the survey were mothers(66%).As expected,food was the main cause of allergic reactions requiring prescription of the auto-injector device.Tree nuts and peanuts were noted to be the most common offending food in these children(62%and 38%,respectively).A doctor provided demonstrations and training on using the auto-injector device to 94%of the parents.More than two-thirds of the parents and caregivers(79%)were deemed knowledgeable on the indication for use of the device.Reluctance to administer the device was expressed by many of the parents,despite their satisfaction with the coaching they received on using the device in the study.CONCLUSION Ongoing coaching and teaching of parents on use of the AAI is paramount.However,this should be carried out together with psychological support to aid the parents to eliminate their hesitancy and acquire sufficient confidence in using the device when needed.Group teaching and sharing experiences is an excellent educational technique in a non-formal setting.Paediatric clinic play therapists can also have a role in needle phobia desensitisation for parents and children.More research is needed to explore the lack of empowerment and other reasons behind their fear and anxiety in using the device to plan effective interventions.
文摘The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.
文摘The most common digestive system(DS)cancers,including tumors of the gastrointestinal tract(GIT)such as colorectal cancer(CRC),gastric cancer(GC)and esophageal cancer(EC)as well as tumors of DS accessory organs such as pancreatic and liver cancer,are responsible for more than one-third of all cancerrelated deaths worldwide,despite the progress that has been achieved in anticancer therapy.Due to these limitations in treatment strategies,oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity.These studies led to new molecular target-driven therapeutic approaches.Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3(B7-H3)among the most common cancers of the GIT,including CRC,GC,and EC,whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal.This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms,and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways,such as Janus kinase 2/signal transducer and activator of transcription 3,phosphatidylinositol 3-kinase/protein kinase B,extracellular signal-regulated kinase,and nuclear factor-κB.B7-H3 exerts an important role in progression,metastasis and resistance to anticancer therapy in these tumors.In addition,the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response.Accordingly,it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response,impaired tumor progression,invasion,angiogenesis,and metastasis and decreased resistance to anticancer therapy.Finally,the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis.In this review,we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.
基金Supported by the National Natural Science Foundation of China,No.81870546the Nanjing Medical Science and Technique Development Foundation,No.YKK17177.
文摘Gestational diabetes mellitus(GDM)is one of the most common metabolic disorders of pregnancy and can cause short-and long-term adverse effects in both pregnant women and their offspring.However,the etiology and pathogenesis of GDM are still unclear.As a metabolic disease,GDM is well suited to metabolomics study,which can monitor the changes in small molecular metabolites induced by maternal stimuli or perturbations in real time.The application of metabolomics in GDM can be used to discover diagnostic biomarkers,evaluate the prognosis of the disease,guide the application of diet or drugs,evaluate the curative effect,and explore the mechanism.This review provides comprehensive documentation of metabolomics research methods and techniques as well as the current progress in GDM research.We anticipate that the review will contribute to identifying gaps in the current knowledge or metabolomics technology,provide evidence-based information,and inform future research directions in GDM.
基金This study was supported by the Science and Technology Innovation-Biomedical Supporting Program of Shanghai Science and Technology Committee(19441904400)Program for artificial intelligence innovation and development of Shanghai Municipal Commission of Economy and Informatization(2020-RGZN-02048).
文摘BACKGROUND:To promote the shared decision-making(SDM)between patients and doctors in pediatric outpatient departments,this study was designed to validate artificial intelligence(AI)-initiated medical tests for children with fever.METHODS:We designed an AI model,named Xiaoyi,to suggest necessary tests for a febrile child before visiting a pediatric outpatient clinic.We calculated the sensitivity,specificity,and F1 score to evaluate the efficacy of Xiaoyi’s recommendations.The patients were divided into the rejection and acceptance groups.Then we analyzed the rejected examination items in order to obtain the corresponding reasons.RESULTS:We recruited a total of 11,867 children with fever who had used Xiaoyi in outpatient clinics.The recommended examinations given by Xiaoyi for 10,636(89.6%)patients were qualified.The average F1 score reached 0.94.A total of 58.4%of the patients accepted Xiaoyi’s suggestions(acceptance group),and 41.6%refused(rejection group).Imaging examinations were rejected by most patients(46.7%).The tests being time-consuming were rejected by 2,133 patients(43.2%),including rejecting pathogen studies in 1,347 patients(68.5%)and image studies in 732 patients(31.8%).The difficulty of sampling was the main reason for rejecting routine tests(41.9%).CONCLUSION:Our model has high accuracy and acceptability in recommending medical tests to febrile pediatric patients,and is worth promoting in facilitating SDM.
基金Scientific Institute for Research and Care Burlo Garofolo, grants No. RC36/08Italian Ministry of Health RF 35/07
文摘From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.
文摘Introduction:Transcatheter closure is an alternative to ventricular septal defect(VSD)occlusion surgery.Nit-Occlud LêVSD coil is a new device yet to be evaluated.The study aimed to evaluate immediate and midterm results after transcatheter closure with the Nit-Occlud LêVSD device.Methods:The retrospective analysis included 30 patients with VSD referred for closure during the period from October 2015 to December 2020.Results:At the time of intervention,the patients’mean age and body weights were 7.5±5.6 years and 29.3±19.1 kg.The majority of the defects had perimembranous location(24/30),four defects had muscular and two outlet subaortic position.The mean effective right-side diameter of the VSDs was 3.6±1.3 mm.Single ventricular fibrillation,device embolization,and hemolysis developed in different patients and were successfully treated.None of the patients had a complete atrioventricular block.The coil was successfully placed in 25/30(83.3%)patients.The majority of the devices were 10 mm×6 mm(11/25)and 12 mm×8 mm(8/25)in size.Two patients required the implantation of a second device.The follow-up period was 2.1±1.4 years.Complete VSD closure was achieved in 48%of cases immediately after the intervention,74%during 2.1±1.6 months after the procedure,and 81%over follow-up.The remaining patients had a trivial residual defect.During the follow-up,approximately one-third of patients developed trivial aortic and mitral valve regurgitation,and half of the patients acquired trace/mild tricuspid regurgitation.Standardized(z-score)left ventricular end-diastolic diameter(0.15±0.37 vs.0.92±0.82,p=0.005)and left atrium dimension(0.47±0.58 vs.1.89±1.11,p=0.005),as well as the left atrium to aortic root ratio(1.2±0.1 vs.1.4±0.2,p=0.005)showed a significant decrease over follow-up related to the period before intervention.Conclusion:Intervention with Nit-OccludLêVSD coil showed appropriate results regarding VSD closure rate,complications,and chamber remodeling.The introduction of this device into clinical practice is a significant step forward in transcatheter perimembranous VSD occlusion.
基金supported by the National Natural Science Foundation of China(Grant Nos.81572556 and 81402139).
文摘Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.
文摘Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival outcomes.The B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,including PC,with low or absent expression in healthy tissues.By modulating various immunological and nonimmunological molecular mechanisms,B7-H3 may influence the progression of PC.However,the impact of B7-H3 on the survival of patients with PC remains a subject of debate.Still,most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in PC.Furthermore,it has been demonstrated that B7-H3 stimulates the migration,invasion,and metastasis of PC cells,and enhances resistance to chemotherapy.In preclinical models of PC,B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibodydependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor site.Finally,PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical studies.This review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research.
文摘Objective: To determine differences in case fatality rates between children with and without Down syndrome. Study design: We used the Pediatric Health Information System (PHIS) database, which includes demographic and diagnostic data from freestanding children’s hospitals. Using Poisson regression, we determined the risk of mortality from sepsis for children with Down syndrome, after controlling for potential confounding factors. Results: A total of 35,645 patients met our inclusion criteria, of which 3936 (11%) died during hospitalization. Altogether, 620 of the included patients also had a diagnosis of Down syndrome; 106 (17%) of these died during hospitalization. Children with Down syndrome had significantly elevated risk of mortality (mortality rate ratio = 1.30; 95%confidence interval = 1.06 to 1.59) after adjusting for potential confounding factors including demographics, pathogens, and concomitant conditions. Conclusions: Children with Down syndrome and sepsis have elevated risk of mortality. These findings have implications for treatment decisions, communications about prognosis, and future research.
文摘Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein- Barr virus (EBV) serology, urine, stool or blood cultures, chest X- ray and tuberculin probe. Results: In 131 (70% ) patients diagnosis was established, and 70 (37.8% )- had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9% ), Kawasaki disease in 12 (6.4% ), malignant diseases in 12 (6.4% ) and miscellaneous conditions in 15 (8.1% ) patients. In the remaining 54 (30% ) patients, diagnosis was not established and most of them had self- limited disease. During the investigation, 26 (14% ) patients developed serious organ dysfunction and five patients (two with virusassociated haemophagocytic syndrome, one with VL and two unknown) died. Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary- care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.
基金supported by grants from the Shanghai Health Commission Clinical Research Project(No.202140161)Shanghai Pudong New Area Science and Technology Development Fund Livelihood Scientific Project(No.PKJ2021-Y43)Key Discipline Program of Shanghai Pudong New Area Health System,China(No.PWZxk2022-25).
文摘To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an essential treatment for various malignant hematological diseases,non-malignant hematological diseases,immunodeficiency diseases,and metabolic diseases in children.[1]During the period of post allo-HSCT immunodeficiency before complete immune reconstitution,transplant recipients having a compromised immune system are more susceptible to infectious diseases than the general population.Therefore,revaccination plays a crucial role in protecting pediatric allo-HSCT recipients from vaccine-preventable diseases.Inactivated vaccines are generally safer and can be administered starting from 6–12 months after transplantation.Live-attenuated vaccines should be administered at least 24 months after transplantation and at least one year after stopping immunosuppressive drugs due to the risk of severe vaccine-induced infection when administered with immunosuppressive agents.[2,3]
基金National Natural Science Foundation of China(823B2087)Shanghai Municipal Health Commission(GWVI-11.2-XD16)+1 种基金National Natural Science Foundation of China Joint Fund Project(U23A20170)Shanghai Municipal Health Commission(Child Neurological and Psychological Development Screening and Intervention Project),Shanghai Key Laboratory of Child Brain and Development(24dz2260100).
文摘Background Developmental delay(DD)poses challenges to children's overall development,necessitating early detection and intervention.Existing screening tools in China focus mainly on children with developmental issues in two or more domains,diagnosed as global developmental delay(GDD).However,the recent rise of early childhood development(ECD)concepts has expanded the focus to include not only those with severe brain development impairments but also children who lag in specific domains due to various social-environmental factors,with the aim of promoting positive development through active intervention.To support this approach,corresponding screening tools need to be developed.Methods The current study used a two-phase design to develop and validate the Parent-Reported Indicator of Developmental Evaluation for Chinese Children(PRIDE)tool.In Phase 1,age-specific milestone forms for PRIDE were created through a survey conducted in urban and rural primary care clinics across four economic regions in China.In Phase 2,PRIDE was validated in a community-based sample.Sensitivity and specificity of both PRIDE and Ages and Stages Questionnaires(ASQ)-3 were estimated using inverse probability weights(IPW)and multiple imputation(MI)to address planned and unplanned missing data.Results In Phase 1 involving a total of 1160 participants aged 1 to 48 months,63 items were selected from the initial item pool to create 10 age-specific PRIDE forms.Our Phase 2 study included 777 children within the same age range.PRIDE demonstrated an estimated sensitivity and specificity of 83.3%[95%confidence interval(CI):56.8%–100.0%]and 84.9%(95%CI:82.8%–86.9%)in the identification of DD.Conclusion The findings suggest that PRIDE holds promise as a sensitive tool for detecting DD in community settings.
基金The study was funded by special grant for Preschool Children’s Health Management from Shanghai Municipal Education Commission,grants from National Natural Science Foundation of China(81874266,81673183)key project from Shanghai Municipal Science and Technology Commission(18411951600).
文摘Background Asthma has been a global problem,especially in children.We aim to evaluate the contemporary prevalence and influencing factors of asthma among children aged 3–7 years in Shanghai,China.Methods A random sample of preschool children was included in this study.The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma.Multivariable logistic regression models were used to evaluate the associations between independent variables and childhood asthma.Results Of 6389 preschool children who were invited to take part in this study,6163(response rate:96.5%)completed the questionnaire and were included in the analysis.The overall prevalence of asthma was 14.6%which increased more than six folds from 2.1%in 1990.Being male,younger age,preterm delivery,being born in spring or autumn,being delivered by elective cesarean section without indication,miscarriage,high socioeconomic status,having allergy history,and exposure to passive smoking,latex paint,and dust were potential risk factors for childhood asthma.Spending more time outdoors(>30 min/day),having indoor plants,and cleaning rooms more frequently were potential protective factors.Conclusions The prevalence of childhood asthma in Shanghai has increased dramatically during the past three decades.The findings about risk and protective factors of childhood asthma could be used to develop appropriate strategies to prevent and control childhood asthma in Shanghai and in other similar metropolitan cities.
基金Supported by NIH grants HL130984,HL140548,and AG061824,a Tier 2 grant from the University of Missourithe Leda J.Sears Foundation.In addition,PEB was supported by FONDECYT grant number 1180397.
文摘Precision medicine requires coordinated and integrated evidence-based combinatorial approaches so that diagnosis and treatment can be tailored to the individual patient.In this context,the treatment approach to mild obstructive sleep apnea(OSA)is fraught with substantial debate as to what is mild OSA,and as to what constitutes appropriate treatment.As such,it is necessary to first establish a proposed consensus of what criteria need to be employed to reach the diagnosis of mild OSA,and then examine the circumstances under which treatment is indicated,and if so,whether and when anti-inflammatory therapy(AIT),rapid maxillary expansion(RME),and/or myofunctional therapy(MFT)may be indicated.
文摘Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses to human society.The overall crude mortality rate is 1-3%.Although pediatric deaths from COVID-19 are rare,they do occur,as over 9,000 children have died from COVID-19 globally to date[1].With the gradual and broad application of COVID-19 vaccines around the world,the rising proportion of cases among children and unvaccinated young adults demands attention.According to World Health Organization surveillance data.
基金supported by grants from the NIH(R01NS102382,R01NS122108,and R01AG073779 to P.J.)M.J.was supported by a post-doctoral fellowship award from the New Jersey Department of Health(CAUT24DFP004)+1 种基金A.V.P.was supported by a graduate trainee T32 fellowship award from the Training in Translating Neuroscience to Therapies program at Rutgers University(T32NS115700)L.C.was supported by the Rutgers HealthAdvance Fund(NHLBI U01HL150852 to L.C.)。
文摘Astroglia are integral to brain development and the emergence of neurodevelopmental disorders.However,studying the pathophysiology of human astroglia using brain organoid models has been hindered by ineficient astrogliogene-sis.In this study,we introduce a robust method for generating astroglia-enriched organoids through BMP4 treatment during the neural differentiation phase of organoid development.Our RNA sequencing analysis reveals that astroglia developed within these organoids exhibit advanced developmental characteristics and enhanced synaptic functions compared to those grown under traditional two-dimensional conditions,particularly highlighted by increased neu-rexin(NRXN)-neuroligin(NLGN)signaling.Cell adhesion molecules,such as NRXN and NLGN,are essential in regulat-ing interactions between astroglia and neurons.We further discovered that brain organoids derived from human embryonic stem cells(hESCs)harboring the autism-associated NLGN3 R451C mutation exhibit increased astroglio-genesis.Notably,the NLGN3 R451C astroglia demonstrate enhanced branching,indicating a more intricate morphol-ogy.Interestingly,our RNA sequencing data suggest that these mutant astroglia significantly upregulate pathways that support neural functions when compared to isogenic wild-type astroglia.Our findings establish a novel astroglia-enriched organoid model,offering a valuable platform for probing the roles of human astroglia in brain development and related disorders.
